We conducted studies on the regulation of gene expression in placenta and liver during development. To study control of pregnancy-specific beta-1- glycoprotein (PSG) gene expression, we have characterized PSG cDNA and genomic clones, immortalized human placental cell lines, and identified the PSG promoters. The two characterized PSG genes, PSGl and PSG1-I, are nearly identical. PSG1 lacking exon 1 encodes five identified type I PSG transcripts and PSG1-I containing a complete transcriptional unit which would encode type II PSG mRNAs lacking an A2 domain, but otherwise identical with the PSG1 transcripts. We showed that -840/-44 region upstream of the translational start of PSG1-I contained cis-acting sequences that direct CAT expression in cultured human placental cells. Sodium butyrate, which stimulated PSG expression, greatly increased CAT expression, indicating that butyrate-induced PSG expression is primarily regulated at the level of gene transcription. In our placental alkaline phosphatase (AP) project, we examined the structure-function relationship of human germ cell AP (GCAP) using site- directed mutagenesis and expression in COS-1 cells. We demonstrated that GCAP is a membrane-bound enzyme located on the outer surface of the plasma membrane. Removing both sugar side chains interferes with enzyme synthesis, but the glycan moieties are not essential for activity, stability, and membrane anchoring of GCAP. We have also determined the structural basis for the differential sensitivity of GCAP and the placental AP (PLAP) to inhibition by L-leucine, EDTA, and heat. These two APs differ by only 7 amino acids. We showed that the critical residue is the amino acid at position 429. GCAP with Gly-429 is strongly inhibited by L- leucine, EDTA, and heat whereas PLAP with Glu-429 is resistant. In our project on liver differentiation, we showed that tyrosine aminotransferase (TAT) expression was stimulated by glucocorticoids and cAMP, but inhibited by retinoic acid. The retinoic acid-mediated TAT inhibition is mainly regulated at the post-transcriptional level. We also immortalized hepatocytes derived from newborn deletion homozygote mice in order to facilitate study of the putative factors on chromosome 7 that affects expression of many liver genes. The immortalized hepatocyte lines in general mimic the behavior of deletion mice and expressed reduced levels of a number of liver genes. However, all affected liver genes tested were responsive to glucocorticoids and cAMP, in contrast to in vivo studies. This may suggest that effects of the deletion on expression of specific liver genes do not cause loss of responsiveness to glucocorticoids and cAMP.